This invention relates to a process for preparing .beta.-lactams by electrochemically deblocking N-substituted .beta.-lactams using anodic oxidation.
Formation of the azetidinone ring is a key step in the chemical synthesis of various .beta.-lactam antibiotics. One synthetic strategy uses p-anisidine as the source of the ring nitrogen atom. Once the azetidinone ring is formed, the p-methoxyphenyl moiety can be removed by oxidative cleavage using oxidizing agents such as ceric ammonium nitrate. For example, G. Cainelli et al., Tetrahedron Lett., 28, 3593-3596 (1987); G. I. Georg et al., J. Am. Chem. Soc., 109, 1129-1135 (1987); and D. R. Kronenthal et al., J. Org. Chem., 47, 2765-2768 (1982). Although frequently producing high yields of deblocked .beta.-lactams, oxidation with ceric ammonium nitrate requires two (and works best with three) equivalents for each mole of substrate. Since ceric ammonium nitrate has a high molecular weight (548), a large-scale reaction requires massive quantities of reagent and generates large quantities of a heavy metal waste material. Furthermore, attempted use of catalytic amounts of ceric ammonium nitrate with a secondary oxidant has been reported to give inferior results. D. R. Kronenthal et al., J. Org. Chem., 47, 2765-2768 (1982). The present invention provides a method of deblocking N-substituted .beta.-lactams in good yields without the economic and environmental disadvantages inherent in traditional chemical oxidation methods.
Electrochemical deblocking of N-alkyl and N-benzyl lactams has been reported. For example, M. Masui et al., Chem. Pharm. Bull., 34, 975-979 (1986); M. Mori and Y. Ban, Heterocycles, 23, 317-323 (1985); and M. Okita et al., Heterocycles, 23, 247-250 (1985). The cited references, however, do not disclose or suggest deblocking .beta.-lactams in which a phenyl or substituted phenyl group is attached directly to the lactam ring nitrogen atom.